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Vertebral compression fractures secondary to osteoporosis can be treated with vertebral augmentation. Since intraprocedural pain is common during vertebral body endplate manipulation, these procedures are often carried out using conscious sedation or general anesthesia. Research has shown that the vertebral endplates are innervated by the basivertebral nerve, which has been successfully targeted via radiofrequency ablation to treat chronic vertebrogenic lower back pain. With this physiology in mind, we treated ten patients with vertebral compression using intraosseous basivertebral nerve block as the primary intraprocedural analgesia. In this case series, we describe our successful experience with this novel approach.

Increasing soil contamination of arsenic (As) and antimony (Sb) is posing a serious concern to human health. Due to insufficient studies on Sb, the biogeochemical behaviour and plant uptake of Sb are assumed to be similar to that of As. As part of extensive research unravelling As and Sb biogeochemistry and plant uptake, the diffusive gradients in thin films (DGT) technique and sequential extraction procedure (SEP) were applied to evaluate As and Sb uptake by the white icicle radish (Raphanus sativus) cultivated in diluted cattle dip soils contaminated with As only and diluted mining soils contaminated with both As and Sb under agricultural conditions. Labile As and Sb in these soils measured by DGT (CDGT), soil solution (Csol), and SEP (CSEP-labile), were compared with As and Sb bioaccumulation in R. sativus tissues. Regardless of contamination sources and measurement techniques, the results showed that As was consistently more labile than Sb although total As concentrations in two soil types were lower than total Sb. Labile As in cattle dip soils was higher than that in mining soils, although there were no significant differences in soil As concentrations. The analysis of R. sativus tissues revealed that the overall As bioaccumulation was 4.5-fold higher than for Sb, and that As translocation to shoots was limited. In contrast, considerable Sb translocation to shoots was observed. The As and Sb bioaccumulation were strongly correlated with their CSEP-labile, CDGT, and Csol (R2 = 0.87-0.99), demonstrating the effectiveness of these techniques in predicting As and Sb in the white icicle radish. Compared with the cherry bell radish previously studied, the white icicle radish exhibited higher bioaccumulation factors (BAF) for Sb, but lower BAF for As, and lower translocation of As and Sb to shoots, providing understanding of how As and Sb are accumulated by radish cultivars. Refereed/Peer-reviewed

Elevated concentrations of As and Sb impact environmental quality and human health. In this study total and bioavailable As and Sb were measured from recently and historically contaminated soils and the phytotoxicity of these soils was evaluated with Ipomoea aquatica (35-d exposure from germination) using biomass, length of plant tissues and photosynthetic efficiency. As and Sb were both present within the soil (co-contaminated). The bioavailable As and Sb in soils were determined by a Sequential Extraction Procedure (SEP) and compared to total soil concentrations and bioaccumulation in the edible parts of I. aquatica. For both As and Sb, bioavailable concentrations increased proportionally with the total soil concentrations and greater bioavailability in recently contaminated soil was observed. Tissue dry mass and length drastically reduced with increasing total and SEP-bioavailable As and Sb soil concentrations. The total soil concentration was a less sensitive measure of the phytotoxicity of As and Sb than the bioavailable fraction. Shoot length was inhibited by 50% (EC50) at bioavailable As concentrations of 80–96 mg kg−1 in both recently and historically contaminated soils; however, bioavailable Sb EC50 for shoot length was achieved at lower bioavailable concentrations, 96 (42–219) and 12 (7–19) mg kg−1 in recently contaminated soils and historically contaminated soils, respectively. Shoot biomass was inhibited by 50% (EC50) at bioavailable As concentrations of 11 (4–30) and 49 (37–65) mg kg−1 in recently and historically contaminated soils, respectively whereas this occurred at much lower bioavailable Sb concentrations, 2–5 mg kg−1 in both recently and historically contaminated soils. Aging is important in contaminated soils, it decreases the lability of As and Sb and hence their bioavailability to agricultural plants, thus posing a lower risk of exposure of these metalloids to humans through agricultural plants grown in contaminated soils.

Connected cars are a rapidly growing segment of Internet of Things (IoT). While they already use cellular networks to support emergency response, in-car WiFi hotspots and infotainment, there is also a push towards updating their firmware over-the-air (FOTA). With millions of connected cars expected to be deployed over the next several years, and more importantly persist in the network for a long time, it is important to understand their behavior, usage patterns, and impact --- both in terms of their experience, as well as other users. Using one million connected cars on a production cellular network, we conduct network-scale measurements of over one billion radio connections to understand various aspects including their spatial and temporal connectivity patterns, the network conditions they face, use and handovers across various radio frequencies and mobility patterns. Our measurement study reveals that connected cars have distinct sets of characteristics, including those similar to regular smartphones (e.g. overall diurnal pattern), those similar to IoT devices (e.g. mostly short network sessions), but also some that belong to neither type (e.g. high mobility). These insights are invaluable in understanding and modeling connected cars in a cellular network and in designing strategies to manage their data demand.

The enrichment of soil arsenic (As) and antimony (Sb) is putting increasing pressure on the environment and human health. The biogeochemical behaviour of Sb and its uptake mechanisms by plants are poorly. understood and generally assumed to be similar to that of As. In this study, the lability of As and Sb under agricultural conditions in historically contaminated soils was assessed. Soils were prepared by mixing historically As and Sb-contaminated soil with an uncontaminated soil at different ratios. The lability of As and Sb in the soils was assessed using various approaches: the diffusive gradients in thin films technique (DGT) (as C-DGT), soil solution analysis, and sequential extraction procedure (SEP). Lability was compared to the bioaccumulation of As and Sb by various compartments of radish (Raphanus sativus) grown in these soils in a pot experiment. Irrespective of the method, all of the labile fractions showed that both As and Sb were firmly bound to the solid phases, and that Sb was less mobile than As, although total soil Sb concentrations were higher than total soil As. The bioassay demonstrated low bioaccumulation of As and Sb into R. sativus due to their low lability of As and Sb in soils and that there are likely to be differences in their mechanisms of uptake. As accumulated in R. sativus roots was much higher (2.5-21 times) than that of Sb, while the Sb translocated from roots to shoots was approximately 2.5 times higher than that of As. As and Sb in R. sativus tissues were strongly correlated with their labile concentrations measured by DGT, soil solution, and SEP. These techniques are useful measures for predicting bioavailable As and Sb in the historically contaminated soil to R. sativus. This is the first study to demonstrate the suitability of DGT to measure labile Sb in Soils. Refereed/Peer-reviewed

We consider the problem of managing Firmware Over-The-Air (FOTA) updates for cars at a massive scale over a cellular network. This problem is constrained by factors like large number of cars, a need to perform updates quickly and securely, ability to do the update anywhere and any time, and delivering the often large update without harming the network. We present a scheduling approach for managing large FOTA downloads in a cellular network that combines historical network load with car usage and location analytics. The proposed approach uses a combination of heuristics and an optimized scheduler and applies them to schedule the admission of cars to download FOTA. Using real network data from a large cellular provider that includes a million cars and nearly a billion radio-level network connections, we show that our scheduling approach is feasible and practical. We also show that it is possible to manage FOTA even when device and network models use high levels of aggregation over time. Simulation results show that our method improves over random uncontrolled approaches by (i) reducing median download startup delay by 48%, (ii) reducing the number of cars that don't complete the update by 10% and most importantly, (iii) reducing the load in busy cells by up to 37%.

Seed dormancy is one of the most crucial process transitions in a plant's life cycle. Its timing is tightly controlled by the expression level of the Delay of Germination 1 gene (DOG1). DOG1 is the major quantitative trait locus for seed dormancy in Arabidopsis and has been shown to control dormancy in many other plant species. This is reflected by the evolutionary conservation of the functional short alternatively polyadenylated form of the DOG1 mRNA. Notably, the 3' region of DOG1, including the last exon that is not included in this transcript isoform, shows a high level of conservation at the DNA level, but the encoded polypeptide is poorly conserved. Here, we demonstrate that this region of DOG1 contains a promoter for the transcription of a noncoding antisense RNA, asDOG1, that is 5' capped, polyadenylated, and relatively stable. This promoter is autonomous and asDOG1 has an expression profile that is different from known DOG1 transcripts. Using several approaches we show that asDOG1 strongly suppresses DOG1 expression during seed maturation in cis, but is unable to do so in trans Therefore, the negative regulation of seed dormancy by asDOG1 in cis results in allele-specific suppression of DOG1 expression and promotes germination. Given the evolutionary conservation of the asDOG1 promoter, we propose that this cis-constrained noncoding RNA-mediated mechanism limiting the duration of seed dormancy functions across the Brassicaceae.

The current and the new generation of Internet of Things (IoT) devices present several challenges, among them the software update of legacy and new devices using wireless connections. In this paper, we study a problem of scheduling massive Firmware-Over-The-Air updates for millions of connected cars. We model this problem as a new generic problem called Time- and Machine-Dependent Scheduling Problem (TMDSP) that resembles project scheduling problems with variable-intensity activities. In the TMDSP, jobs, machine utilization, and production rates vary over time. In each period, a given job can be executed by a subset of machines with different capacities and production rates. The objective is to deploy a feasible schedule with minimum total completion time. We explore solving the problem using several approaches among than Biased Random-Key Genetic Algorithm (BRKGA), Iterated Local Search (ILS), Simulating Annealing (SA), two variations of Tabu Search (TB), and traditional genetic algorithms (TGA), in addition to a Mixed Integer Programming (MIP) model. We test the proposed approaches on a synthetic benchmark and very large real instances in IoT space. While using a commercial solver and the MIP model, we are able to solve only a few real instances (with, at most, 1,976 cars and 9,116 sectors); on the other hand, BRKGA presents significantly better results when compared to ILS, MIP solver and a simple multi-start heuristic.

Accurate tRNA processing is crucial for human mitochondrial genome expression, but the mechanisms of mt-tRNA cleavage and the key enzymes involved in this process are poorly characterized. At least two activities are required for proper mt-tRNA maturation: RNase P cleaving precursor molecules at the 5' end and tRNase Z at the 3' end. In human mitochondria only RNase P has been identified so far. Using RT-PCR and northern blot analyses we found that silencing of the human ELAC2 gene results in impaired 3' end of mt-tRNAs. We demonstrate this for several mitochondrial tRNAs, encoded on both mtDNA strands, including tRNA (Val) , tRNA (Lys) , tRNA (Arg) , tRNA (Gly) , tRNA (Leu(UUR)) and tRNA (Glu) . The silencing of the MRPP1 gene that encodes a subunit of mtRNase P resulted in inhibition of both 5' and 3' processing. We also demonstrate the double mitochondrial/nuclear localization of the ELAC2 protein using immunofluorescence. Our results indicate that ELAC2 functions as a tRNase Z in human mitochondria and suggest that mt-tRNase Z preferentially cleaves molecules already processed by the proteinaceous mtRNase P.

Protein complexes responsible for RNA degradation play important role in three key aspects of RNA metabolism: they control stability of physiologically functional transcripts, remove the unnecessary RNA processing intermediates and destroy aberrantly formed RNAs. In mitochondria the post-transcriptional events seem to play a major role in regulation of gene expression, therefore RNA turnover is of particular importance. Despite many years of research, the details of this process are still a challenge. This review summarizes emerging landscape of interplay between the Suv3p helicase (SUPV3L1, Suv3), poly(A) polymerase and polynucleotide phosphorylase in controlling RNA degradation in human mitochondria.

The mechanism of human mitochondrial RNA turnover and surveillance is still a matter of debate. We have obtained a cellular model for studying the role of hSuv3p helicase in human mitochondria. Expression of a dominant-negative mutant of the hSUV3 gene which encodes a protein with no ATPase or helicase activity results in perturbations of mtRNA metabolism and enables to study the processing and degradation intermediates which otherwise are difficult to detect because of their short half-lives. The hSuv3p activity was found to be necessary in the regulation of stability of mature, properly formed mRNAs and for removal of the noncoding processing intermediates transcribed from both H and L-strands, including mirror RNAs which represent antisense RNAs transcribed from the opposite DNA strand. Lack of hSuv3p function also resulted in accumulation of aberrant RNA species, molecules with extended poly(A) tails and degradation intermediates truncated predominantly at their 3′-ends. Moreover, we present data indicating that hSuv3p co-purifies with PNPase; this may suggest participation of both proteins in mtRNA metabolism.

Background: Data on the effect of laparoscopic cholecystectomy (LC) on bowel function are controversial. The aim of this study was to determine the incidence of postcholecystectomy diarrhoea (PCD) and to identify patient characteristics that can be used as predictors in daily practice. Methods: In 100 consecutive patients who underwent LC, data were obtained from clinical records and telephone survey 6–12 months postoperatively using standardized questionnaire. Results: Postoperatively, 19 patients had diarrhoea, including 17 with new onset. Two patients with preoperative and postoperative diarrhoea were excluded from further analysis. Of 98 patients (mean age 58.1 ± 19.4 years; 62 women) 34 were younger than 50 years, 33 were overweight (BMI 25–29.9 kg/cm2) and 29 were obese (BMI >30 kg/cm2). PCD was significantly associated with younger age (odds ratio (OR) 3.4; 95% confidence interval (CI) 1.16–9.96; P = 0.026), higher BMI (OR 1.1; 95%CI 1.01–1.18; P = 0.019) and food intolerance postoperatively (OR 3.4; 95%CI 1.18–10.08; P = 0.025). PCD was most common with combination of two or three of the following factors: age 25 kg/cm2. The highest risk of developing PCD was observed in obese men younger than 50 (OR 26.1), and the lowest in persons aged >50 years with BMI

A gas chromatographic-mass spectrometric (GC-MS) method in positive ion chemical ionization mode in combination with a solid phase extraction was optimized for new-generation antidepressants and their metabolites in postmortem blood, brain tissue, and hair. Twelve antidepressants and their active metabolites (i.e., mirtazapine, viloxazine, venlafaxine, citalopram, mianserin, reboxetine, fluoxetine, fluvoxamine, sertraline, maprotiline, melitracen, paroxetine, desmethylfluoxetine, desmethylmianserin, desmethylmirtazapine, desmethylsertraline, desmethylmaprotiline, desmethylcitalopram, and didesmethylcitalopram) could be quantified. In this article, in addition to the validation of the GC-MS method, four postmortem cases are discussed to demonstrate the usefulness of the described method in forensic toxicology. In these cases, sertraline, fluoxetine, citalopram, and trazodone in combination with their active metabolites were quantified. Blood concentrations ranged from subtherapeutic to toxic concentrations, while brain to plasma ratios ranged from 0.8 to 17. Hair concentrations ranged from 0.4 to 2.5 ng/mg depending on the compound and hair segment.

HLA-B27 transgenic rats develop spontaneous colitis under specific pathogen-free conditions (SPF) but germ-free rats remain disease-free, emphasizing a role for intestinal bacteria in the pathogenesis of chronic intestinal inflammation. Prebiotics are dietary substances that affect the host by stimulating growth and/or activity of potentially health promoting bacteria. The aims of this study were to investigate whether prebiotics can prevent colitis in SPF HLA-B27 rats, and secondly, to explore mechanisms of protection. SPF HLA-B27 transgenic rats received orally the prebiotic combination long-chain inulin and oligofructose (Synergy 1), or not, prior to the development of clinically detectable colitis. After seven weeks, cecal and colonic tissues were collected for gross cecal scores (GCS), histologic inflammatory scores (scale 0-4), and mucosal cytokine measurement. Cecal and colonic contents were collected for analysis of the gut rnicrobiota by PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and fluorescent in-situ hybridization (FISH), and analysis of short-chain fatty acid composition. Prebiotic treatment significantly decreased GCS and inflammatory histologic scores in the cecum and colon. Prebiotic treatment also decreased cecal IL-I beta, but increased cecal TGF-beta concentrations. Inulin/oligofructose altered the cecal and colonic PCR-DGGE profiles, and FISH analysis showed significant increases in cecal Lactobacillus and Bifidobacterium populations after prebiotic treatment compared with water-treated rats. In conclusion, the prebiotic combination Synergy I reduced colitis in HLA-B27 transgenic rats, which effect was associated with alterations to the gut microbiota, decreased tissue proinflammatory cytokines and increased immunomodulatory molecules. These results show promise for prebiotics as primary or adjuvant maintenance therapy for chronic inflammatory bowel diseases.

Inter-domain routing connects individual pieces of Internet topology, creating an integral, global data delivery infrastructure. Currently, this critical function is performed by the Border Gateway Protocol (BGP) version 4 [RFC1771]. Like all routing protocols, BGP is vulnerable to instabilities that reduce its effectiveness. Among the causes of these instabilities are those which are maliciously induced. Although there are other causes, e.g., natural events and network anomalies, this thesis will focus exclusively on maliciously induced instabilities. Most current models that attempt to predict a BGP routing instability confine their focus to either macro- or micro-level metrics, but not to both. The inherent limitations of each of these forms of metric gives rise to an excessive rate of spurious alerts, both false positives and false negatives. It is the original intent of this thesis to develop an improved BGP instability prediction model by statistically combining BGP instability metrics with user level performance metrics. The motivation for such a model is twofold. 1) To provide sufficient prior warning of impending failure to facilitate proactive protection measures. 2) To improve warning reliability beyond existing models, by demonstrably reducing both false positives and false negatives. However, our analysis of actual network trace data shows that a widely used BGP instability metric, the total number of update messages received in a time period, is not a good indicator of future user level performance. http://archive.org/details/predictingcatast109451642 Civilian, Department of Defense Approved for public release; distribution is unlimited.